Key Takeaways & Executive Findings
- •• Bioelectricity and endogenous electric fields are critical biophysical factors in bone remodeling and regeneration, providing a foundation for electroactive therapeutic strategies. • Electroactive hybrid biomaterials (EHBs) combine electroactive properties with biocompatibility and biodegradability, offering biomimetic scaffolds that promote osteogenic differentiation and extracellular matrix synthesis. • Self-powered systems, including triboelectric and piezoelectric nanogenerators and photovoltaic devices, enable wireless, battery-free electrical stimulation for bone tissue engineering, overcoming limitations of conventional ES devices. • Simulating the target tissue's electrophysiological microenvironment is crucial for effective bone repair; future research should focus on integrating EHBs with self-powered systems and addressing challenges such as long-term stability and clinical translation.
Abstract
The incidence of large bone defects caused by traumatic injury is increasing worldwide, and the tissue regeneration process requires a long recovery time due to limited self-healing capability. Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration. Inspired by bioelectricity, electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix, thereby accelerating bone regeneration. With ongoing advances in biomaterials and energy-harvesting techniques, electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue. In this review, we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue. Next, we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering. Finally, we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.
1. Introduction
Bone diseases, ranging from arthritis and osteoporosis to bone cancer and fractures, represent significant challenges and burdens in modern society [1–4]. The increasing incidence of large bone defects caused by traumatic injuries, coupled with the limited self-healing capability of bone tissue, necessitates the development of advanced therapeutic strategies [5]. Traditional methods for bone repair, such as autografts and allografts, often come with limitations, including donor site morbidity, limited availability, and risk of immune rejection [6]. Consequently, there is a pressing need for innovative approaches that can enhance bone regeneration and repair.
One promising avenue in bone therapeutics is the integration of electroactive hybrid biomaterials (EHBs) and self-powered systems [7, 8]. These technologies leverage the intrinsic bioelectrical properties of bone tissue to create biomimetic environments that promote bone healing. The concept of bioelectricity in bone tissue is not new [9]; it has long been recognized that electrical signals play a crucial role in bone remodeling and regeneration. Natural bone is a composite material primarily composed of hydroxyapatite and collagen, which exhibits specific bioelectric phenomena under different physiological conditions. These phenomena include dielectric properties, pyroelectricity, ferroelectricity, and piezoelectricity in dry bone [10, 11], as well as stream potential and electroosmosis in wet bone [12–14].
Given the critical role of bioelectricity in bone tissue, researchers have explored the use of exogenous electric fields (Exo-EFs) to mimic or modulate Endo-EFs for treating bone diseases. Exogenous electrical stimulation (ES) has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix, thereby accelerating bone regeneration. The US Food and Drug Administration has approved the use of ES as a non-pharmacological treatment for fracture healing, with devices available in both invasive and non-invasive forms. The development of EHBs that simulate the electrophysiological microenvironment of bone tissue has attracted significant attention. EHBs combine the properties of electroactive materials with biocompatibility and biodegradability, making them suitable for bone tissue engineering. Conductive biomaterials (CBMs), such as metallic CBMs and metal nanoparticles, facilitate the regu
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Shichang Liu, Farid Manshaii, Jinmiao Chen, Xinfei Wang, Shaolei Wang, Junyi Yin, Ming Yang, Xuxu Chen, Xinhua Yin, Yunlei Zhou (2024). Unleashing the Potential of Electroactive Hybrid Biomaterials and Self-Powered Systems for Bone Therapeutics. Nano-Micro Letters. https://doi.org/10.1007/s40820-024-01536-9
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Frequently Asked Questions
What are electroactive hybrid biomaterials (EHBs) and how do they aid bone regeneration?
EHBs are biomaterials that combine electroactive properties (such as piezoelectricity, conductivity, or pyroelectricity) with biocompatibility and biodegradability. They mimic the natural electrophysiological microenvironment of bone tissue, promoting osteogenic differentiation of cells and enhancing extracellular matrix synthesis, thereby accelerating bone regeneration.
How do self-powered systems contribute to bone tissue engineering?
Self-powered systems, such as triboelectric and piezoelectric nanogenerators and photovoltaic devices, generate electrical stimulation from mechanical or light energy without external power sources. They can be integrated into scaffolds or implants to provide localized, on-demand electrical cues that enhance bone healing, offering a wireless and battery-free approach.
What is the role of bioelectricity in bone tissue?
Bioelectricity refers to endogenous electrical phenomena in bone, including piezoelectricity, pyroelectricity, and streaming potentials. These signals are critical for bone remodeling and regeneration, influencing cellular activities such as proliferation, differentiation, and matrix production.
What are the challenges in translating electroactive biomaterials and self-powered systems to clinical use?
Challenges include ensuring long-term stability and biocompatibility of materials, achieving precise control over electrical stimulation parameters, scaling up production, and conducting rigorous preclinical and clinical trials to demonstrate safety and efficacy in humans.
How does electrical stimulation (ES) promote bone healing?
ES induces osteogenic lineage commitment of stem cells, enhances extracellular matrix synthesis, and modulates cellular signaling pathways. It can also improve angiogenesis and reduce inflammation, collectively accelerating bone regeneration. FDA-approved ES devices are used for fracture healing.
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